1. Field of the Invention
This invention relates to a process for the preparation of cyanohydrins. More particularly, it relates to an improved process for the preparation of optically active (S)-cyanohydrins, useful as intermediates in the preparation of known pyrethroid insecticides, comprising reacting aldehydes with hydrocyanic acid in the presence of S-oxynitrilase enzyme.
2. Statement of Related Art
The process of reacting aldehydes with hydrocyanic acid in the presence of the enzyme oxynitrilase and the solvent diisopropyl ether to form optically active cyanohydrins is known, for example, from U.S. Pat. No. 4,859,784 to Effenberger et. al., which is incorporated herein by reference. As taught by this reference, the reaction is carried out with the enzyme in an immobilized form, such as bound to the surface of glass spheres, ion-exchange resins, or particles of cellulose, in the form of a slurry which must first be filtered out of solution before the product can be recovered. While effective for the purpose intended, this method is characterized by only a single pass of reactants through the immobilized enzyme, which pass-through takes 5 to 6 days to complete. Similarly, Australian Patent Application 38104/89, to Kula et. al., teaches a like process in which the enzyme, S-oxynitrilase, is derived from a particular source (Sorohum bicolor). In this process, there is used in one embodiment, an acrylic bead to immobilize the enzyme, i.e., Eupergit.RTM. C (Rohm, Darmstadt), a commercially available acrylic bead which is useful suspended in the reaction medium or in a column. In either event, it must be used only in an aqueous system to avoid any attack on the acrylic bead by various organic solvents. Moreover, in this latter process employing bound enzymes, a yield of about 85 wt. % is obtained, but only after a 3-day continuous run, using as the aldehyde 4-hydroxybenzaldehyde. See also U.S. Pat. No. 5,008,192 to Neidermeyer; European Patent 326,063; U.S. Pat. No. 3,862,030; and German Offen. 3823864 A-1, which are cumulative to or correspond to the above U.S. and Australian references.
In each of the above patents, reference is made to an "enzyme-diaphragm-reactor." However, as the corresponding technical literature reveals, (see, for example, "Engineering Aspects of Enzyme Engineering," and footnotes 16 and 17 therein, i.e., Kragel et al., Ann. N.Y. Aca. Sci., 613, pp. 167-175, (1990), and Vasic-Racki et. al., Appl. Microbiol. Biotechnol. 31, pp. 215-222 (1989)), such reactors represent nothing more than a series of containers separated by filtration membranes to which the enzyme is physically impervious. Thus, in this type of reactor the reaction is carried out in a solution containing a dispersed enzyme with which the reactants must then eventually come in contact by diffusion.
The use of polymeric membrane reactors to bind enzymes is generally known from U.S. Pat. Nos. 4,102,746, and 4,169,014, both to Bruce S. Goldberg. See also, "A Novel Immobilized Enzyme Reactor System," Bruce S. Goldberg, presented at the 27th Annual Spring Symposium Session on Non-Conventional Reactor Systems, AICHE, East Brunswick, N.J., May 10, 1984, which further describes the membrane reactors of these two U.S. patents. These latter two patents and the AICHE presentation of May 10, 1984 are also incorporated herein by reference.